TRIM5 Acts as More Than a Retroviral Restriction Factor 英文参考文献.docVIP

Viruses 2011, 3, 1204-1209; doi:10.3390/v3071204 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Commentary TRIM5 Acts as More Than a Retroviral Restriction Factor Suresh de Silva and Li Wu * Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA; E-Mail: suresh.de-silva@ * Author to whom correspondence should be addressed; E-Mail: wu.840@; Tel.: +1-614-292-5408; Fax: +1-614-292-6473. Received: 20 June 2011; in revised form: 7 July 2011 / Accepted: 10 July 2011 / Published: 15 July 2011 Abstract: The retrovirus restriction factor TRIM5α blocks post-entry infection of retroviruses in a species-specific manner. As a cellular E3 ubiquitin ligase, TRIM5α binds to the retroviral capsid lattice in the cytoplasm of an infected cell and accelerates the uncoating process of retroviral capsid, thus providing a potent restriction to HIV-1 and other retrovirus infections. The precise mechanism by which this restriction is imposed remains under scrutiny, and evidence is lacking to link the E3 ubiquitin ligase activity of TRIM5α to its ability to restrict retrovirus infection. In a recent study, Pertel and colleagues have uncovered the link between the two, providing compelling evidence to suggest that following the interaction with the retroviral capsid, TRIM5 triggers an antiviral innate immune response by functioning as a pattern recognition receptor [1]. This unique function of TRIM5 is dependent on its association with the E2 ubiquitin- conjugating enzyme complex UBC13-UEV1A and subsequent activation of the TAK1 kinase complex and downstream genes involved in innate immune responses. These findings have defined a novel function for TRIM5 as a pattern recognition receptor in innate immune recognition and provided valuable mechanistic